Neisseria meningitidisa capsulated, Gram-negative bacterium, is a cause of life-threatening invasive bacterial infection, especially in young children. The organism can be classified into at least 13 serogroups based on chemically and antigenically distinctive polysaccharide capsules. Among them, serogroups A, B, C, W-135and Y account for virtually all pathogenic isolates. Despite several decades of research, no effective vaccine that protects against all meningococcal strains is available, and diseases caused by N. meningitidismeningitis and septicemia, remain a serious public health problem throughout the world ENRfu (Peltola, Drugs 55: 347-366, 1998). The failure in development of effective vaccines is possibly attributed to the high antigenic diversity of the pathogen. The currently licensed vaccine is polysaccharide-based which does not include the serogroup B capsular polysaccharide, due to the poor immunogenicity of the latter substance (Frasch, Meningococcal vaccines: past, present and future. In: Meningococcal Disease. Cartwright K. (Ed.) Wiley Press, New York, USA: 145-157, 1995.). Therefore effective vaccine against disease caused by serogroup B strains, the organisms responsible for the majority of meningococcal infections in many countries, is still not available ENRfu (Verheul et al., Microbiol Rev 57:34-49, 1993).
For development of effective vaccines against serogroup B meningococci, most research has focused on the outer membrane proteins (OMPs). Of the five major OMP classes, class I OMP (also named PorA) has attracted the most attentions. This is because that PorA is expressed by most meningococci and is highly immunogenic in humans following infection or immunization (Guttormen et al., Infect. Immun 62:1437, 1994; Clasassen et al., Vaccine 14:1001, 1996; van der Ley and Poolman, Infect Immun. 60:3156, 1992). Moreover, specific antibodies induced by PorA exhibit both bactericidal activity and opsonic function (Aase et al., Scand J Immunol 47:388-396, 1998; Lehmann et al., Infect. Immun. 67:2552, 1999). However, the high degrees of antigenic and phase variation of PorA have limited the effectiveness of PorA-based vaccines to the vaccine-type strains (Fischer et al., Vaccine 17: 2377-2383, 1999). Broadened protection may be achieved by combining different PorA subtypes. For example, a hexavalent PorA vaccine composed of the most prevalent PorA variants found in the Netherlands and Western Europe has been developed (Claassen et al., 1996, Vaccine 14:1001-1008; Peeters et al, 1996, Vaccine 14:1009-1015). Nevertheless, the observation that different PorA phenotypes can emerge rapidly after its epidemic spread (Jelfs et al., Clin. Diagn. Lab. Immunol. 7:390-395, 2000; Martin et al., Vaccine 18:2476-2481, 2000) has to be considered in the development of PorA-based vaccine.
To create vaccines with a broad spectrum of protection, it is important to identify surface proteins which are highly conserved in different strains. Several proteins meet the criteria have been reported. These include P64k (U.S. Pat. No. 5,286,484), hemoglobin receptor (U.S. Pat. No. 6,121,037), NspA (U.S. Pat. No. 6,287,574 B1), NhhA (U.S. Pat. No. 6,607,729 B2), NMASP (U.S. Pat. No. 6,693,186 B2), NadA (Comanducci et al., J. Exp. Med. 195:1445-1454, 2002), GNA1870 (Masignani et al., J. Exp. Med. 197:789-799, 2003), GNA33GNA992GNA1162GNA1220GNA1946GNA2001 and GNA2132in which GNA1870GNA33GNA1162GNA1946 and GNA2132 are lipoproteins identified by whole genome sequencing (Pizza et al., Science 287:1816-1820, 2000). Despite the discovery of these proteins, it is still desirable to isolate more surface proteins of N. meningitidis which in combination with others may enhance the vaccine efficacy.